The German coach took charge of his first home match since he was appointed in May, but after solid results on their US tour, including a win over Real Madrid, the Catalans crumbled at the Olympic Stadium.
Monaco took the lead early in the second half of Barcelona's traditional Joan Gamper Trophy curtain-raiser through Lamine Camara before Breel Embolo swiftly doubled the advantage.
Ilkay Gundogan departed after suffering a blow to the head, while Flick brought on Spain's Euro 2024 star Lamine Yamal to try and spark a flat Barca into life.
The 17-year-old excited briefly but supporters ended up whistling their side after Christian Mawissa smashed home Monaco's third late on.
Barcelona, aiming to snatch the Spanish title back from rivals Real Madrid, start their LaLiga campaign on Saturday with a difficult trip to face Valencia.
Carlo Ancelotti's Blancos, who followed up last season's league and Champions League double by signing French superstar Kylian Mbappe, begin their domestic campaign on Sunday against Real Mallorca.
